ABSTRACT The propensity of glioma cells to invade brain is a vexing problem that limits the effectiveness of all current therapies. Thus, there remains a pressing need to identify new anti-invasive strategies. Accomplishing this will require a detailed understanding of how glioma cells migrate within the brain, and what machinery they use to drive this process. In our earlier work, we determined that the molecular motor myosin II plays an indispensable role in glioma dispersion through brain. However, fundamental questions about this process remain unanswered. First, how do myosin IIA and IIB, the two myosin II isoforms commonly expressed in gliomas, execute the processes underlying brain invasion? Second, how do signal transduction pathways that are frequently dysregulated in gliomas affect the functions of these myosin II isoforms and how redundant are these pathways in stimulating myosin II-dependent tumor invasion? Finally, how do myosin IIA and IIB function contribute to the dispersion of gliomas in tumor-bearing animals? The experiments described in this proposal will explore the advantages and potential limitations of one anti-invasive approach that targets a key element in the machinery gliomas use to invade brain--myosin II.